Platelet factor-4 (PF4) binds to platelets in a reversible fashion. However, binding parameters are greatly influenced by aggregation of purified PF4 molecules. Therefore, a method is needed to recomplex purified PF4 with its native binding protein to keep it in solution in a relativity high concentration. Using preps of complexed PF4, we have demonstrated saturable binding to platelets and have shown that this binding is increased in the presence of equimolar heparin. In contrast, the binding of heparin to platelets appears not to be increased in the presence of PF4. Platelet binding of PF4 and heparin is related to the platelet binding of immunoglobulin G (IgG) from patients with heparin-induced thrombocytopenia. The stoichiometry of the platelet-heparin-PF4-IgG interaction is under investigation.